Spinal Glial Activation Contributes to Postoperative Mechanical Hypersensitivity in the Rat

Unlabelled: The activation of spinal cord microglia and astrocytes after peripheral nerve injury or inflammation contributes to behavioral hypersensitivity. The contribution of spinal cord glia to mechanical hypersensitivity after hind paw incision has not been investigated previously. Male Sprague-Dawley rats underwent a unilateral plantar hind paw incision, and the development of mechanical hypersensitivity was assessed by using von Frey filaments. The activation of spinal cord microglia and astrocytes was measured 1, 2, 3, and 5 days after hind paw incision by using immunohistochemistry. The glial activation inhibitor, fluorocitrate, was administered intrathecally 24 hours after hind paw incision to determine glial involvement in mechanical hypersensitivity. Hind paw incision induced an activation of spinal astrocytes ipsilateral to incision within 24 hours. Both microglia and astrocytes reached a maximum activation 3 days after hind paw incision. Fluorocitrate produced a dose-dependent reduction in mechanical hypersensitivity when administered 24 hours after hind paw incision. Spinal cord glial activation contributes to the mechanical hypersensitivity that develops after hind paw incision.

Perspective: Hind paw incision produces mechanical hypersensitivity that can be alleviated with the inhibition of spinal cord glia. Our results suggest that the activation of spinal cord astrocytes within 24 hours of incision contributes to mechanical hypersensitivity. Therefore, spinal cord astrocytes might represent a novel target for the treatment of postoperative pain.